Understanding nature's design for a nanosyringe

Abstract

Synthetic and natural peptide assemblies can possess transport or conductance activity across biomembranes through the formation of nanopores. The fundamental mechanisms of membrane insertion necessary for antimicrobial or synthetic pore formation are poorly understood. We observe a lipid-assisted mechanism for passive insertion into a model membrane from molecular dynamics simulations. The assembly used in the study, a generic nanotube functionalized with hydrophilic termini, is assisted in crossing the membrane core by transleaflet lipid flips. Lipid tails occlude a purely hydrophobic nanotube. The observed insertion mechanism requirements for hydrophobic-hydrophilic matching have implications for the design of synthetic channels and antibiotics.T he interaction between biological membranes and synthetic or natural macromolecules that have activity through the formation of transmembrane nanopores is intrinsic to the functioning of ion channels (1-8) and antimicrobial peptides (6, 9). It is surprising, therefore, that the insertion mechanism of amphiphilic molecules into (and even across) biomembranes is poorly understood (10-13). The use of fully atomistic computer simulations to probe the interactions of membrane proteins with lipid bilayers is of considerable current interest (8). However, despite many recent successes, such simulations are hampered by the accessible system size and timescale. To glean some insight into possible mechanisms associated with the membrane insertion process we have used molecular dynamics (MD) calculations to study the interaction of tubular macromolecules with a fully hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer in its physiologically relevant liquid-crystalline phase. The calculations we report have been carried out by using a coarse-grain (CG) model, inspired by the model successfully used to study self-organizing surfactant systems (14). The tubular nanostructures we study are generic models for preassembled bundles of membrane-spanning proteins (3, 11), antimicrobial peptides (4), and cyclic peptides (1) and for a synthetic nanosyringe based on functionalizing a carbon nanotube (2, 15). Although many naturally existing ion channels and antimicrobial peptides form pores with a hydrophilic lumen, many systems exist, including viral ion channels, synthetic peptides, and nanodevices, for which the present model should be an adequate description.The present simulations involve molecular systems that represent Ϸ70,000 atoms altogether. Simulations with larger systems have been reported (8,16). The present CG approach, however, allows us to routinely calculate dynamics in the hundreds or thousands of nanoseconds and therefore allows us to study events that take place at longer scales than those currently accessible by all-atom calculations. Methods CG Model. In the CG model (17, 18), each DMPC lipid molecule consists of 13 interaction sites, eight of which are hydrophobic (four for each alkanoyl tail) and five of which are hydrophilic, three for the glycerol moiety ...

Spontaneous insertion of carbon nanotube bundles inside biomembranes: A hybrid particle-field coarse-grained molecular dynamics study

“…So far, experimental methods can provide for these systems only limited information at the molecular scale level. For this reason, several simulation studies involving CNT and lipid bilayers have been reported [17,18,[21][22][23][24][25][26][27]. On the contrary, molecular dynamics simulations based on atomistic or coarse-grained models can provide detailed information on these processes.…”

“…In particular, hydrophobic 4 nanopores [23], fullerenes [24,25], SWCNT [18], and the piercing mechanism of a single CNT into a model membrane [26] have been studies using CG models. The mechanism of spontaneous insertion of short pristine CNTs has been recently studied by Sansom et.…”

Single-Walled Carbon Nanotubes Exhibit Strong Antimicrobial Activity

“…26 Interestingly, results from molecular dynamics simulations can be used to explain the higher antimicrobial activity of smaller-diameter nanotubes such as SWNTs in comparison to that of larger-diameter nanotubes. 10,27 In this study, we postulate that SWNT aggregates caused irrecoverable damage to the E. coli bacteria by physical damage to the outer membrane of the cells, causing the release of intracellular content.…”

Effects of CdSe/ZnS quantum dots covered multi-walled carbon nanotubes on murine embryonicstem cells

“…At the maximum dose tested, this novel nanocomposite reduced ES cell viability by 70%, with a significant fraction of the cells demonstrating molecular evidence of apoptosis. Previously, SWCNTinduced cytotoxicity and apoptosis of HEK293 cells was concluded to result from binding of these nanomaterials to ion channels and cell surface receptors [25]. The authors hypothesized that this event may negatively affect conformation and function of membrane proteins, thus activating cell signaling pathways that enhance apoptosis.…”